JPH0667829B2 - Ibuprofen-containing gelatin soft capsule and method for producing the same - Google Patents

Abstract

Soft gelatin capsules containing a solution of from 15 to 30 parts by weight of ibuprofen in from 70 to 85 parts by weight of polyoxyethylene-polyoxypropylene polymer or in a mixture of from 30 to 76 parts by weight of polyalkylene glycol and from 7 to 40 parts by weight of a surfactant have a very rapid and high bio-availability of the active ingredient. The active ingredient is not re-precipitated therefrom by aqueous media such as artificial gastric juice.

Description

TECHNICAL FIELD The present invention relates to a soft gelatin capsule containing ibuprofen and a method for producing the same.

Prior Art Ibuprofen, 2- (4-isobutylphenyl) propionic acid, is known as a drug having an anti-inflammatory and analgesic effect [eg, Martindale (Ma
rtindale), The Extra Huamaco Poea (The
Extra Pharma-copoeia) 28th edition, p256 (1982)]. This drug is used to treat rheumatoid arthritis or other inflammatory diseases in the joints, soft tissue rheumatism or gout. Ibuprofen, due to its analgesic effect,
It has also been widely used as an analgesic for headache, toothache or dysmenorrhea.

The requirement for a suitable medical treatment for sedation of acute pain is the rapid onset of action of the drug, which is only due to the rapid release of the active ingredient, as well as good bioavailability. To be achieved.

The dosage form of ibuprofen for enteral administration which has been commercially available so far has been a solid preparation such as a sugar-coated tablet or a coated tablet. German Patent Publication (Application published unexamined) No. 2832
Nos. 280 and 3124014 disclose suspensions of ibuprofen, where ibuprofen is present as an aluminum salt. From the composition of the suspension, as well as the dose required to take an effective amount of ibuprofen,
Such suspensions are unsuitable for encapsulation. DE-A-3340347 and EP-A-00070714 disclose gelatin soft capsules containing ibuprofen suspended in a carrier in addition to other dosage forms. All such formulations need to meet high standards of physical properties of the active ingredient, such as particle size and specific surface area, in order to ensure high availability of ibuprofen. In the case of commercially available dosage forms (tablets, sugar-coated tablets), even slight changes in the tableting pressure for mixing, machine type, etc. will affect the physical properties of the active ingredient particles and increase their bioavailability. It will decrease, so
It is necessary to strictly comply with the manufacturing conditions.

Structure and object of the present invention The present invention provides a medical treatment which can be easily ingested and which contains an active amount of ibuprofen in a carrier, which is easy to manufacture and can rapidly exhibit high activity. The purpose is to do. Ibuprofen is soluble in some physiologically compatible solvents, but it precipitates immediately when a small amount of water is added to the solution or when the solution is placed in an aqueous solvent such as artificial gastric juice. Therefore, even if such a solution is taken orally, when it enters the stomach, it is not absorbed rapidly because the aqueous contents of the deposit precipitate ibuprofen.

The present inventors have found that ibuprofen can react with polyoxyethylene-polyoxypropylene polymers or polyalkylene glycols and surfactants (te
It has been found that it dissolves well in a mixture with nside) and that the obtained solution remains in solution even when cooled to room temperature. Even more surprisingly, the solution is
It has also been found that no precipitation occurs, especially when placed in artificial gastric juice, and thus ibuprofen is rapidly and completely absorbed from this solution. Moreover, it has been found that gelatin soft capsules can be filled with these solutions by a method known per se. This dosage form is advantageous over all previously known dosage forms for ibuprofen in that the active ingredient is rapidly absorbed on ingestion. In order to achieve the effect of the present invention, after synthesizing the active ingredient, it is treated with a costly galenic treatment (ga).
lenic processing). Alternatively, high bioavailability can be achieved with a high degree of reliability and reproducibility. Therefore, the action appears quickly and surely.

More specifically, the effect of the present invention is that ibuprofen is added to a mixture of 85 to 70 parts by weight of polyoxyethylene-polyoxypropylene polymer or 76 to 30 parts by weight of polyalkylene glycol and 7 to 40 parts by weight of a surfactant. 15
Achieved by preparing ibuprofen-containing gelatine soft capsules filled with a solution containing ~ 30 parts by weight. Up to 3 parts of 1,2-propylene glycol may be added to facilitate the manufacturing process and increase solubility. Even in such a case, the above-mentioned various characteristics are not deteriorated upon contact with an aqueous medium such as artificial gastric juice.

Another advantage of the solution according to the invention is that ibuprofen can be additionally suspended in this solution up to a maximum of 40 parts by weight, resulting in a relatively small dosage form, even at high doses. , It is easy to administer. Such dosage forms should be considered, especially when used to treat rheumatic diseases.

A particularly suitable solvent for the present invention is polyoxyethylene.
Is a poly-oxypropylene polymer. Relative molecular quality
The polymer in an amount of 1400 to 2000 is preferred. Like that
The product is, for example, a registered trademark Pluronic )of
Below, a commercially available product can be obtained. They are menstruation
Of the gelatin soft cap.
Suitable as a raw material for manufacturing cells.

Further, suitable solvents include polyalkylene glycol 30-
A mixture of 76 parts by weight and 7 to 40 parts by weight of surfactant is included. Polyethylene glycol and polypropylene glycol are preferred and their relative molecular mass is 300-630.
It is preferably in the range of. These products are also commercially available and physiologically compatible and can be used for the purposes of the present invention. When using polyalkylene glycols, it is necessary to additionally use 7 to 40 parts by weight of surfactant in order to avoid reprecipitation of the active ingredient by an aqueous medium such as artificial gastric juice. Suitable surfactants include, for example, polyoxyethylene glycerol trihydroxystearate, polyoxyethylene (C _12-18 ) _-aliphatic alcohol ethers, polyoxyethylene stearate, polyoxyethylene sorbitan mono (C _{12- 18} ) -fatty acid esters, as well as polyoxyethylene-polyoxypropylene polymers.
The number of ethylene oxide units in the polyoxyethylene glycerol trihydroxystearate is preferably 35 to 65, in polyoxyethylene (C _12-18 ) _-fatty alcohol ethers it is preferably 15 to 25 . The number of ethylene oxide units in polyoxyethylene stearate is preferably 15 to 45, and that in polyoxyethylene sorbitan mono (C _12-18 ) fatty acid esters is preferably 15 to 25.

According to the invention, to dissolve ibuprofen in a solvent, the solvent is warmed to 45-65 ° C. Only at this temperature the dissolution rate of ibuprofen reaches a sufficient value. Reprecipitation does not occur when the solution is cooled to room temperature. If a larger amount of ibuprofen is to be filled in gelatine soft capsules, it is advisable to suspend the active ingredient in this solution at room temperature.
At room temperature, a further 40 parts by weight of ibuprofen can be suspended in this solution, which is then filled into gelatine soft capsules. When using a mixture of polyalkylene glycol and surfactant, each of these components should
Mix at temperatures up to 80 ° C until homogenized and cool the resulting mixture to about 50-60 ° C. At this latter temperature, ibuprofen is added and allowed to dissolve.

A second object of the present invention is a method for producing a gelatin soft capsule containing ibuprofen, which comprises:
Dissolve 30 parts by weight in a mixture of polyoxyethylene-polyoxypropylene polymer 70 to 85 parts by weight or polyalkylene glycol 30 to 76 parts by weight and a surfactant 7 to 40 parts by weight at a temperature of 45 to 65 ° C. The present invention provides a method, which comprises cooling the obtained solution to room temperature and filling it into a gelatin soft capsule by a method known per se.

Thirdly, the present invention relates to 15 to 30 parts by weight in a mixture of 70 to 85 parts by weight of polyoxyethylene-polyoxypropylene polymer or 30 to 76 parts by weight of polyalkylene glycol and 7 to 40 parts by weight of a surfactant. It relates to a method of using a solution containing parts by weight of ibuprofen for the production of gelatin soft capsules.

Hereinafter, the gelatin soft capsule according to the present invention and the method for producing the same will be described in detail with reference to examples.

Example 1 270.62 g of polyethylene glycol 400 and polyoxyethylene
Len- (40) -glycerol trihydroxy stearate
To [Cremova (Cremophor ) RH40: BASF] 29.26g
And 1,2-propylene glycol 6.12g at 70 ℃ -80 ℃
These are mixed under stirring to prepare these mixtures. this
The mixture is cooled to 50 ° C and, with stirring, 90.00 g of ibuprofen
Add little by little. The resulting solution was cooled to room temperature
After that, it is filled into a gelatin soft capsule having an appropriate size. This
0.880 g of the solution contains 200 mg of ibuprofen
There is.

Example 2 264.50 g of polyethylene glycol 400 and polyoxyethylene
Len- (40) -glycerol trihydroxy stearate
To [Cremova (Cremophor ) RH40; BASF] 29.26g
Are mixed under stirring at 70 ° C to 80 ° C, and these mixtures are mixed.
Prepare. The mixture is cooled to 50 ° C and stirred under stirring.
Lofuen 90.00 g, then 1,2-propylene glycol 1
Add 2.24g little by little. Cool the resulting solution to room temperature
After that, fill it into an appropriate size gelatin soft capsule.
It The solution 0.880 g contained ibuprofen 200 mg.
ing.

Example 3 90.00 g of ibuprofen was stirred under stirring at 50-60 ° C.
Dissolve 4.74 g of polyethylene glycol 400 at this temperature
And polyoxyethylene- (40) -glycerol trihirate
Droxystearate (cremophor (Cremopho
r ) RH40; BASF] 24.86 g and 1,2-propylene glycol 1
0.40 g is added sequentially. After cooling the solution to room temperature,
Fill into soft gelatin capsules of suitable size. Solution 0.
200 mg of ibuprofen is contained in 778 g.

Example 4 270.62 g of polypropylene glycol 425 and polyoxyethylene
Tylene- (40) -glycerol trihydroxy steare
Red (Cremopher (Cremophor ) RH40; BASF] 29.2
6g and 1,2-propylene glycol 6.12g with 70 ℃ ~ 80
These mixtures are prepared by mixing at 0 ° C. with stirring.
The mixture is cooled to 50 ° C. and, with stirring, ibuprofen 9
Add 0.00g little by little. Cool the resulting solution to room temperature
After that, fill it into an appropriate size gelatin soft capsule.
It The solution 0.880 g contained ibuprofen 200 mg.
ing.

Example 5 270.70 g of polyethylene glycol 600 and polyoxyethylene
Len- (40) -glycerol trihydroxy stearate
To [Cremova (Cremophor ) RH40; BASF] 29.30g
And 6.00 g of 1,2-propylene glycol at 60 ℃ -70 ℃
These are mixed under stirring to prepare these mixtures. this
The mixture is cooled to 50 ° C and, with stirring, 90.00 g of ibuprofen
Add little by little. The resulting solution was cooled to room temperature
After that, it is filled into a gelatin soft capsule having an appropriate size. Melting
The liquid 0.880 g contains 200 mg of ibuprofen
It

Example 6 Polyoxyethylene-polyoxypropylene polymer 19
00 (Pluronic (Pluronic ) L35, Y & T
Wyandotte Chemic
als corp.)] 30.773 kg, polyoxyethylene- (40)
-Glycerol trihydroxystearate [Kremov
Ah (Cremophor ) RH40; BASF] 3.325 kg and 1,2-
0.675 kg of propylene glycol under stirring at 60 ° C,
Mix and mix the resulting mixture under stirring with ibuprofen 10.2
Add 27kg little by little. Cool the resulting solution to room temperature
Then, it is filled into a gelatin soft capsule of an appropriate size.
The solution 0.880 g contains 200 mg of ibuprofen
It

Example 7 Polyoxyethylene-polyoxypropylene polymer 15
00 (Pluronic (Pluronic ) L42, Y & T
Wyandotte Chemic
als corp.)] 391.24 g, polyoxyethylene- (40)-
Glycerol trihydroxystearate (cremophor
- (Cremophor ) RH40; BASF] 39.18g and 1,2-p
Mix 9.00g of ropylene glycol at 60 ℃ with stirring
It 90.00 g of ibuprofen was added to the obtained mixture with stirring.
Add little by little. After cooling the resulting solution to room temperature,
Fill into soft gelatin capsules of suitable size. Solution 0.
882 g contains 150 mg of ibuprofen.

Example 8 Polyoxyethylene-polyoxypropylene polymer 19
00 (Pluronic (Pluronic ) L35, Y & T
Wyandotte Chemic
als corp.)] 276.73 g and polyoxyethylene- (40)-
Glycerol trihydroxystearate (cremophor
- (Cremophor ) RH40; BASF] 29.77g and 60 ℃
And mix with stirring, and the resulting mixture is stirred with ibuprof
Add 90.00 g of EN little by little. Cool this solution to room temperature
After that, fill it into an appropriate size gelatin soft capsule.
It The solution 0.880 g contained ibuprofen 200 mg.
ing.

Example 9 Polyoxyethylene-polyoxypropylene polymer 19
00 (Pluronic (Pluronic ) L35, Y & T
Wyandotte Chemic
als corp.)] 306.00 g under stirring at 60 ° C. with ibupro
Add 90.00g of Fuen little by little. The resulting solution is allowed to reach room temperature.
After cooling with, fill in soft gelatin capsules of appropriate size.
Fill. The solution (0.880 g) contains 200 mg of ibuprofen.
It is rare.

Example 10 Polyoxyethylene-polyoxypropylene polymer 15
00 (Pluronic (Pluronic ) L42, Y & T
Wyandotte Chemic
als corp.)] 306.00 g under stirring at 60 ° C. with ibupro
Add 90.00g of Fuen little by little. The resulting solution is allowed to reach room temperature.
After cooling with, fill in soft gelatin capsules of appropriate size.
Fill. The solution (0.880 g) contains 200 mg of ibuprofen.
It is rare.

Example 11 Polyoxyethylene-polyoxypropylene polymer 20
00 (Pluronic (Pluronic ) L44, Y & T
Wyandotte Chemic
als corp.)] 306.00 g under stirring at 60 ° C. with ibupro
Add 90.00g of Fuen little by little. The resulting solution is allowed to reach room temperature.
After cooling with, fill in soft gelatin capsules of appropriate size.
Fill. The solution (0.880 g) contains 200 mg of ibuprofen.
It is rare.

Example 12 149.94 g of polyethylene glycol 400, polyoxyethylene
Len-polyoxypropylene polymer 1900 [Pluronics
Ku (Pluronic ) L35, W & T Chemicals
 Corporate (Wyandotte Chemicals corp.)] 1
49.94 g and 1,2-propylene glycol 6.12 g at 60 ° C
Mix under stirring at 70 ° C and stir in the resulting mixture.
Below, add 90.00 g of ibuprofen little by little. Got
Allow the solution to cool to room temperature and then soften it to the appropriate size.
Fill capsules. In 0.880 g of solution, ibuprofen
2,000 mg is included.

Example 13 270.62 g of polyethylene glycol 400, polyoxyethylene
Len- (20) -stearyl alcohol [BRIJ 78, Ato
Atlas Chemical I
ndustries)] 29.26 g and 1,2-propylene glycol
Mix 6.12g under stirring at 60 ℃ to 70 ℃ and cool to 50 ℃.
After that, in the resulting mixture, under stirring, ibuprofen
Add 90.00g little by little. Cool the resulting solution to room temperature
After that, fill it into an appropriate size gelatin soft capsule.
It The solution 0.880 g contained ibuprofen 200 mg.
ing.

Example 14 Polyoxyethylene-polyoxypropylene polymer 19
00 (Pluronic (Pluronic ) L35, Y & T
Wyandotte Chemic
als Corp.) 270.62g, polyoxyethylene- (30) -s
Tearate [MYRJ 51 、 Atlas Chemical Indus
Triys (Atlas Chemical Industries)] 29.26 g and
And 6.12-g of 1,2-propylene glycol at 60 ° C to 70 ° C
After mixing with stirring and cooling the resulting mixture to 50 ° C.,
With stirring, 90.00 g of ibuprofen are added in small portions. Got
The cooled solution is allowed to cool to room temperature and then gelatinized to the appropriate size.
Fill soft capsules. In 0.880 g of solution, ibupro
Contains 200 mg of Fuen.

Example 15 Polyoxyethylene-polyoxypropylene polymer 19
00 (Pluronic (Pluronic ) L35, Y & T
Wyandotte Chemic
als Corp.) 270.62g, polyoxyethylene- (20) -s
Tearyl alcohol [BRIJ 78, Atlas Chemical
Industries (Atlas Chemical Industries)] 29.
26 g and 1,2-propylene glycol 6.12 g at 60 ° C to 70
Mix under stirring at ℃, cool the resulting mixture to 50 ℃
After that, add 90.00 g of ibuprofen little by little with stirring.
It After cooling the obtained solution to room temperature,
Fill into soft gelatin capsules. In 0.880 g of solution,
Contains 200 mg of ibuprofen.

Example 16 270.62 g of polyethylene glycol 400, polyoxyethylene
Len- (60) -glycerol trihydroxy stearate
To [Cremova (Cremophor ) RH60; BASF] 29.26g
And 1,2-propylene glycol 6.12g at 60 ℃ ~ 70 ℃
Mix under stirring at room temperature and cool the resulting mixture to 50 ° C.
Then, with stirring, 90.00 g of ibuprofen are added little by little.
After cooling the resulting solution to room temperature, it is sized appropriately.
Fill into soft Latin capsules. In 0.880 g of solution, Eve
Contains 200 mg of profene.

Example 17 Polyoxyethylene-polyoxypropylene polymer 19
00 (Pluronic (Pluronic ) L35, Y & T
Wyandotte Chemical
s Corp.) 270.62g, polyoxyethylene- (60) -gly
Cerrole trihydroxystearate (cremophor
(Cremophor ) RH60; BASF] 29.26g and 1,2-propyi
Mix 6.12g of ren glycol at 60 ℃ -70 ℃ with stirring
The resulting mixture was cooled to 50 ° C and then stirred under stirring.
Add 90.00 g of profene little by little. The resulting solution in the chamber
After cooling to high temperature, soft gelatin capsule of appropriate size
To fill. 200 mg of ibuprofen in 0.880 g of solution
It is included.

Example 18 Polyoxyethylene-polyoxypropylene polymer 15
00 (Pluronic (Pluronic ) L42, Y & T
Wyandotte Chemic
als Corp.)] 270.62 g, polyoxyethylene- (20)-
Sorbitan monostearate (Tween (Twee
n ) 60, Atlas Chemical Industries (Atl
as Chemical Industries)] 29.26 g and 1,2-propene
Mix 6.12g of ren glycol at 60 ℃ -70 ℃ with stirring
The resulting mixture was cooled to 50 ° C and then stirred under stirring.
Add 90.00 g of profene little by little. The resulting solution in the chamber
After cooling to high temperature, soft gelatin capsule of appropriate size
To fill. 200 mg of ibuprofen in 0.880 g of solution
It is included.

Example 19 Polyoxyethylene-polyoxypropylene polymer 19
00 (Pluronic (Pluronic ) L35, Y & T
Wyandotte Chemic
als Corp.)] 270.62g, polyoxyethylene (40) -g
Lycerol trihydroxystearate (cremophor
(Cremophor ) RH40; BASF] 29.26g and 1,2-Pro
Mix 6.12 g of pyrene glycol at 60 ℃ -70 ℃ with stirring.
And the resulting mixture was cooled to 50 ° C and stirred under stirring.
Add 90.00 g of buprofen little by little. In addition, obtained
Finely ground ibupro at 15-20 ° C.
Suspend 90.00 g of fuen. Then obtained in this way
Fill the resulting suspension into soft gelatin capsules of appropriate size.
Fill. 400 mg of ibuprofen was added to 1.080 g of the suspension.
include.

Example 20 Polyoxyethylene-polyoxypropylene polymer 19
00 (Pluronic (Pluronic ) L35, Y & T
Wyandotte Chemic
als Corp.)] 202.97 g, polyoxyethylene (40) -g
Lycerol trihydroxystearate (cremophor
(Cremophor ) RH40; BASF] 21.95 g and 1,2-pro
Mix 4.59 g of pyrene glycol at 60 ℃ -70 ℃ with stirring.
And the resulting mixture was cooled to 50 ° C and stirred under stirring.
Add 67.50 g of buprofen little by little. In addition, obtained
Finely ground ibupro at 15-20 ° C.
Suspend 112.50 g of Fueng. Then get in this way
Put the resulting suspension into soft gelatin capsules of appropriate size.
Fill. 400 mg of ibuprofen in 0.910 g of suspension
It is included.

The release of ibuprofen from the soft gelatin capsules according to the present invention was examined by a dissolution test in pepsin-free artificial gastric juice (USPXX) 4 according to the method described in USP XX Fifth Supplement. The concentration of ibuprofen was determined by measuring the UV spectrum at 231 nm. As a comparative sample, a commercially available sugar-coated tablet and solutions A and B shown below were used. Solution A contains in 0.880 g 200 mg ibuprofen, 666.4 mg propylene glycol 400 and 13.6 mg 1,2-propylene glycol. Also, Solution B contains 0.880 g of ibuprofen 200 mg.
And 680.0 mg of propylene glycol 400.

Table 1 shows the ibuprofen release rate (%) from the soft gelatin capsules according to the present invention and the comparative preparation.

In addition to this Table I, FIGS. 1A-D show the time course of release from several representative formulations. As can be readily seen from these, ibuprofen is released substantially more rapidly from the gelatin soft capsules of the present invention than commercially available dragees or capsules containing comparable amounts of comparative solutions. It Moreover, the release of ibuprofen from the comparative capsules stopped at 48% or less after 2 hours, whereas the release from the formulation of the invention reached up to 100%.

The capsule of the present invention, a commercially available sugar-coated tablet, and EP-OS0070.
The bioavailability of ibuprofen in the 714 (Example 2) capsules was tested in 4 volunteers. Each subject was administered with a capsule or dragee containing 200 mg of ibuprofen; after a certain period of time, a blood sample was collected from the subject and the ibuprofen content in blood was measured. The average value of these measurement results is shown in FIG.
~ D.

The bioavailability of a drug from a formulation is understood to represent the rate and extent to which the medical care translocates into the circulating blood (E. Muts
chler) Alznai Mitztel-Wilkungen, Weizsenshyaft Ritzier Huerla-Guz Gezershaft
mbH, Stuttgart (Arzneimittel-Wirkungen, Wissen
schaftliche VerlagsgesellschaftmbH, Stuttgart) 198
1]. FH Dost (Grandla Gen der Fuarmako Kinetic, Gyoji Taem Vuellag, Shyattgart (Grandlagen der Pharmakokin
According to etik Georg Thiem Vorlag, Shuttgart) 1968], the area (AUC, area under the curve) surrounded by the curve showing the blood level and the time axis corresponds to the amount of the substance in the living body. This value makes it possible to compare the bioavailability of substances released from the different applied formulations. AUC values were calculated from the curves showing the economical blood level changes shown in FIGS. 2A to 2D, and the relative bioavailability of ibuprofen was calculated based on the obtained values. It was shown to.

From Table 2, the gelatin soft capsule of the present invention has a bioavailability of ibuprofen of 55% to 50% of that of commercially available sugar-coated tablets.
It can be seen that there is an improvement of 78%, or 22% to 40% or more of the capsule preparation shown in the prior art. Furthermore, as is apparent from the blood concentration curves in FIGS. 2A to 2D, it can be seen that the capsules of the present invention release the active ingredient more rapidly and vigorously as compared with the conventional preparation. As described above, according to the capsule of the present invention, ibuprofen can be released more rapidly and at a high release rate, and a high degree of bioavailability can be achieved. Therefore, the ibuprofen-containing preparation can be obtained.

Table 3 shows the ibuprofen release (mg) from the capsules of Examples 19 and 20 compared to that from the commercially available dragees, the medium volume being increased for technical reasons during the measurement. There is no so, when high doses of active ingredient are high, saturation is reached quickly. In this case as well, it is clearly recognized that the capsule of the present invention exhibits a superior action to the commercially available sugar-coated tablets. The obtained values are shown in FIG.

[Brief description of drawings]

1A, B, C, and D are graphs schematically showing the time-dependent changes in the release rate (%) of ibuprofen from various preparations. In FIG. , Is Example 1, ◯-◯ is a capsule for solution A, and in FIG. 1B, Δ-Δ is Example 4. Is a capsule according to Example 13, ◯-◯ is a commercially available sugar-coated tablet, and in FIG. 1C, Δ-Δ is Example 6, Example 14, and ○-○ are capsules of Example 10, Fig. 1D.
In the example, Δ-Δ represents Example 8, Is the capsule of Example 17, and ○-○ represents a commercially available sugar-coated tablet. FIG. 2 is a graph schematically showing the time course of blood level (μg / ml) after ingestion of 200 mg of ibuprofen, where A is a commercially available tablet and B is a capsule of EP-OS0070714. Figure 2-2 shows 200m ibuprofen
3 is a graph schematically showing the time course of blood level (μg / ml) after ingestion, where C is the capsule of Example 1 and D
Represents the capsule of Example 6. FIG. 3 is a graph schematically showing the time course of the release (mg) of ibuprofen, where Δ-Δ is the capsule of Example 19, Is the capsule of Example 20, ○-○ is a commercially available sugar-coated tablet (400 m
g).

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Claims (8)

[Claims] 1. A polyoxyethylene-polyoxypropylene polymer comprising 70 to 85 parts by weight, or 30 to 76 parts by weight of a polyalkylene glycol and 7 to 40 parts by weight of a surfactant.
A gelatin soft capsule containing ibuprofen, which comprises a solution of 15 to 30 parts by weight of ibuprofen in a mixture of 70 to 85 parts by weight. 2. A soft gelatin capsule according to claim 1, which further comprises up to 3 parts by weight of 1,2-propylene glycol. 3. In addition to dissolved ibuprofen, a further 40
The gelatin soft capsule according to claim 1 or 2, which contains up to 1 part by weight of suspended ibuprofen. 4. As a surfactant, polyoxyethylene glycerol trihydroxystearate, polyoxyethylene (C _12-18 ) _-aliphatic alcohol ethers, polyoxyethylene stearate, polyoxyethylene sorbitan mono (C _{12- 18} ) -Fatty acid ester, polyoxyethylene-polyoxypropylene polymer, or a mixture thereof is contained.
Item 3. A gelatin soft capsule according to any one of items. 5. A method for producing a soft gelatin capsule containing ibuprofen, which comprises, at 45 ° C. to 65 ° C., 15 to 30 parts by weight of ibuprofen, 70 to 85 parts by weight of polyoxyethylene-polyoxypropylene polymer, or polyalkylene glycol. Dissolved in a mixture of 70 to 85 parts by weight of 30 to 76 parts by weight and a surfactant of 7 to 40 parts by weight, cooling the solution to room temperature, and filling the gelatin soft capsules by a method known per se. how to. 6. A process according to claim 5, characterized in that up to 3 parts by weight of 1,2-propylene glycol are added to the solvent. 7. Process according to claim 5, characterized in that after cooling, the solution is further suspended in up to 40 parts by weight of ibuprofen. 8. As a surfactant, polyoxyethylene glycerol trihydroxystearate, polyoxyethylene (C _12-18 ) _-aliphatic alcohol ethers, polyoxyethylene stearate, polyoxyethylene sorbitan mono (C _{12- 18} ) -Fatty acid ester, polyoxyethylene-polyoxypropylene polymer, or a mixture thereof is used, The method according to any one of items 5 to 7.